Nanoparticle-Loaded Hydrogel for the Light-Activated Release and Photothermal Enhancement of Antimicrobial Peptides

Abstract

Rising concerns over multidrug-resistant bacteria have necessitated an expansion to the current antimicrobial arsenal and forced the development of novel delivery strategies that enhance the efficacy of existing treatments. Antimicrobial peptides (AMPs) are a promising antibiotic alternative that physically disrupts the membrane of bacteria, resulting in rapid bactericidal activity; however, clinical translation of AMPs has been hindered by their susceptibility to protease degradation. Through the co-loading of liposomes encapsulating model AMP, IRIKIRIK-CONH2 (IK8), and gold nanorods (AuNRs) into a poly­(ethylene glycol) (PEG) hydrogel, we have demonstrated the ability to protect encapsulated materials from proteolysis and provide the first instance of the triggered AMP release. Laser irradiation at 860 nm, at 2.1 W cm–2, for 10 min led to the photothermal triggered release of IK8, resulting in bactericidal activity against Gram-negative Pseudonomas aeruginosa and Gram-positive Staphylococcus aureus. Furthermore, by increasing the laser intensity to 2.4 W cm–2, we have shown the thermal enhancement of AMP activity. The photothermal triggered release, and enhancement of AMP efficacy, was demonstrated to treat two rounds of fresh S. aureus, indicating that the therapeutic gel has the potential for multiple rounds of treatment. Taken together, this novel therapeutic hydrogel system demonstrates the stimuli-responsive release of AMPs with photothermal enhanced antimicrobial efficacy to treat pathogenic bacteria.

Peptide Gelators to Template Inorganic Nanoparticle Formation

“…NP incorporation into nanogels holds promise in innovative therapy and targeted delivery for reduced side-effects [11,111]. Alternatively, multiple components can be combined together, as recently demonstrated in the case of a PEG hydrogel with gold nanorods, liposomes, and an antimicrobial peptide for the photo-triggered release of the latter [112]. Furthermore, metal coordination can also affect the properties of peptide-based supramolecular hydrogels in ways that are not always straightforward to predict, and further understanding in this area will be important [113].…”

Evaluating Phospholipid‐Functionalized Gold Nanorods for In Vivo Applications

“…of cancer [5][6][7] and for thermally triggered drug release in the treatment of pathogens. [8] AuNPs can be synthesized such that they possess strong absorbance within the "near-infrared biological window." Within this range of wavelengths, light can penetrate biological tissue by several centimeters.…”

“…[ 1–4 ] Their strong plasmonic response and high photothermal efficiency have made them particularly appealing as photothermal conversion agents in the therapy and imaging of cancer [ 5–7 ] and for thermally triggered drug release in the treatment of pathogens. [ 8 ] AuNPs can be synthesized such that they possess strong absorbance within the “near‐infrared biological window.” Within this range of wavelengths, light can penetrate biological tissue by several centimeters. This enables them to be used as in vivo nano‐heaters to thermally ablate cancerous tissue with minimal heat generation in the intermediate tissue along the light path.…”

Cyanobacteria and Eukaryotic Microalgae as Emerging Sources of Antibacterial Peptides

“…In addition, the implementation of nanotechnological vehiculation of the peptides improve their bioavailability by targeting the peptide at the right anatomical or cellular location, preventing peptide waste and off-target effects, as well as avoiding the proteolytic degradation of the peptide. In addition, vehicle degradation may sustain or control a gradual delivery of the peptide at the right site [65][66][67][68]. A greater decrease in the number of peptides entering the pipeline for peptide development is achieved by in silico selection of new and improved prediction tools for candidate selection based on an expected higher effectiveness or decreased toxicity [69][70][71][72][73].…”